The invention relates to a method of ultrasound imaging of organs and tissues by detection of ultrasound backscatter from a region which may contain nonlinear scatterers such as microbubbles used as a contrast agent, the method comprising projecting an ultrasound beam to a zone of tissue to be imaged, receiving the echo reflected from the tissue as a radiofrequency response signal, processing the radiofrequency response into a demodulated video output signal, storing the output in a video scan converter, and scanning the tissue to produce a video image of the region under investigation. The invention also comprises a system for ultrasonic imaging of organs or tissues which may contain nonlinear scatterers such as microbubbles used as a contrast agent, the system comprising an ultrasonic probe for transmitting and receiving ultrasonic signals, signal processing means, means for storing the processed signals and a display element. Use of the system for imaging of organs, tissues and blood vessels is also disclosed.
Wide acceptance of ultrasound as an inexpensive non-invasive diagnostic technique coupled with rapid development of electronics and related technology has brought about numerous improvements to ultrasound equipment and ultrasound signal processing circuitry. Ultrasound scanners designed for medical or other uses have become cheaper, easier to use, more compact, more sophisticated and more powerful instruments. However, the changes of acoustic impedance occurring within the living tissue are small and the absorption of ultrasound energy by different types of tissue (blood vessels, organs, etc.) are such that some diagnostic applications remain unmet challenges, despite these technical developments. This situation changed considerably with the development and introduction of administrable ultrasound contrast agents. Introduction of contrast agents made from stabilized suspensions of gas microbubbles or microballoons into the bloodstream and organs to be investigated have demonstrated that better and more useful ultrasound images of organs and surrounding tissue may be obtained with ultrasound equipment. Thus, pathologies in organs like the liver, spleen, kidneys, heart or other soft tissues are becoming more readily recognizable, opening up new diagnostic areas for both B-mode and Doppler ultrasound and broadening the use of ultrasound as a diagnostic tool.
Recently, ultrasound techniques, i.e. scanners, electronic circuitry, transducers and other hardware and software components are showing great progresses in their abilities to exploit, to a fuller extent, the specific properties of ultrasound contrast agents. This is made possible by the vision by ultrasound instrument manufacturers of the vast potential offered by these contrast agents towards more accurate diagnosis, thanks to enhanced imaging capabilities and quantification of blood flow and perfusion. Thus, what was almost independent developments of these related segments of the field are now providing opportunity to draw on synergies offered by studies in which the electronic/ultrasound characteristics of the apparatus and the physical properties of the contrast agent are combined. A few examples of such studies reported improvements from specific agents/equipment combinations, such as harmonic contrast imaging. These synergies are thus opening new areas of experimentation, innovation, and search of more universal methods for producing greater tissue resolution, better image and greater versatility of ultrasound as a diagnostic technique. There is no doubt that, provided their implementation is kept relatively simple, these will be widely accepted.
An attempt towards improved ultrasound imaging is described in WO-A-93/12720 (Monaghan) which discloses a method of imaging of a region of the body based on subtracting ultrasound images obtained prior to injection of a contrast agent from the images of the same region obtained following administration of the contrast agent. Based on this response subtraction principle, the method performs superposition of images obtained from the same region prior to and after administration of the contrast agent, providing an image of the region perfused by the contrast agent freed from background image, noise or parasites. In theory, the method described is capable of providing a good quality images with enhanced contrast. However, in practice, it requires maintenance of the same reference position of the region imaged for a long period of time, i.e. long enough to allow injection and perfusion of the contrast agent and maintenance of an enormous amount of data. Therefore the practical implementation of the method is very difficult if not impossible. The difficulty is partly due to inevitable internal body movements related to breathing, digestion and heart beat, and partly due to movements of the imaging probe by the ultrasound operator. Most realtime imaging probes are commonly handheld for best perception, feedback and diagnosis.
Interesting proposals for improved imaging of tissue containing microbubble suspensions as contrast agent have been made by Burns, P., Radiology 185 P (1992) 142 and Schrope, B. et al., Ultrasound in Med. and Biol. 19 (1993) 567. There, it is suggested that the second harmonic frequencies generated by non-linear oscillation of microbubbles be used as imaging parameters. The method proposed is based on the fact that normal tissue does not display nonlinear responses to the same extent as microbubbles, and therefore the second harmonics method allows for contrast enhancement between the tissues with and without contrast agent. Although attractive, the method has its shortcomings, as its application imposes several strict requirements. Firstly, excitation of the fundamental xe2x80x9cbubble-resonancexe2x80x9d frequency must be achieved by fairly narrow-band pulses, i.e. relatively long tone bursts of several radio-frequency cycles. While this requirement is compatible with the circuits and conditions required by Doppler processing, it becomes hardly applicable in the case of B-mode imaging, where the ultrasound pulses must be of very short duration, typically one-half or one-cycle excitation. In this case, insufficient energy is converted from the fundamental frequency to its xe2x80x9csecond-harmonicxe2x80x9d, and thus the B-mode imaging mode cannot greatly benefit from this echo-enhancing method. Secondly, the second harmonic generated is attenuated, as the ultrasound echo propagates in tissue on its way back to the transducer, at a rate as determined by its frequency, i.e. at a rate significantly higher than the attenuation rate of the fundamental frequency. This constraint is a drawback of the xe2x80x9charmonic-imagingxe2x80x9d method, which is thus limited to propagation depths compatible with ultrasound attenuation at the high xe2x80x9csecond-harmonicxe2x80x9d frequency. Furthermore, in order to generate echo-signal components at twice the fundamental frequency, xe2x80x9charmonic imagingxe2x80x9d requires non-linear oscillation of the contrast agent. Such behavior imposes the ultrasound excitation level to exceed a certain acoustic threshold at the point of imaging (i.e. at a certain depth in tissue). During nonlinear oscillation, a frequency conversion takes place, causing in particular part of the acoustic energy to be converted from the fundamental excitation frequency up to its second harmonic. On the other hand, that level should not exceed the microbubble burst level at which the microbubbles are destroyed, and hence harmonic imaging will fail due to the destruction of the contrast agent in the imaging volume. The above constraints require that the imaging-instrument be set-up in such a way as to ensure the transmit-acoustic level to fall within a certain energy band: high enough to generate second harmonic components, but low enough to avoid microbubble destruction within a few cycles.
Thus, methods which treat electronic echo signals during normal realtime (xe2x80x9con the flyxe2x80x9d) investigations are those most desirable, allowing better imaging and wider use of ultrasound diagnostic imaging. Such methods are based on an enhancement of the echoes signals received from the regions imaged, using signal processing functions which are designed to enhance the contrast between regions containing contrast agent from those without contrast agent, on the basis of nonlinear or frequency-dependent parameters, would be simple to use and implement in new instrument designs.
U.S. Pat. Nos. 5,632,277 and 5,706,819 already disclose methods and apparatus for the detection and imaging of harmonic echo components from microbubble-based contrast agents in blood. These methods utilize first and second ultrasound pulses that are alternatively transmitted into the medium being imaged. The first and second ultrasound pulses are amplitude modulated signals in the radiofrequency range, the first ultrasound pulse differing only in sign (polarity) from the second ultrasound pulse transmitted. The echo signals generated by these successive pulses are stored in memory and combined by adding them so that the linear components cancel, leaving only the nonlinear component to be imaged. Accordingly, since tissue generally reflects less harmonic components than microbubbles, such processing enables the microbubble echoes of the contrast agent to be received with a high signal to noise ratio.
In these known approaches, for each xe2x80x9cline-of-sightxe2x80x9d, or in other words for each ultrasound beam steering and focusing properties, a minimum of two successive pulses is required to cancel echoes from tissues while preserving significant signals of echoes from microbubbles. The radio-frequency echo signals are stored in a temporary memory following excitation of each successive pulses.
Alternative methods have been proposed in U.S. Pat. No. 5,961,463, or WO 99/30617 according to which, by alternating the polarity or otherwise coding the successive excitation conditions and taking the sum, difference or other combinations of these rf-echo signals, essentially zero signals are produced from linear reflectors other than the microbubbles, while echo signals from microbubbles produce non-linear signals that can be used to construct images with great sensitivity and enhanced contrast between microbubbles and tissues not containing a significant number of microbubbles.
There are several disadvantages common to these techniques. Firstly, because of the finite propagation velocity of sound in tissues, a time interval of several hundred microseconds must elapse between successive transmit pulses, in order for the echoes from the deepest regions of interest to return to the ultrasound probe before a following transmit pulse can be applied. This requirement limits the achievable frame rate, which is reduced in a proportion depending on the number of pulses fired in each direction, compared to similar imaging conditions without contrast-specific transmit coding. Secondly, the bubbles can move significant distances in the blood vessels in the time interval between pulses. Because of that, the resulting processing is sensitive not only to nonlinear scattering by microbubbles, but also to decorrelation due to movement between pulses. Thirdly, since the bubbles are excited successively by interrogating pulses, they can be destroyed or in other ways altered between successive pulses. As a consequence, the resulting images, Doppler or other signals are not purely dependent on the nonlinear particularities of microbubbles, but also depend on these other possible effects and artefacts.
These techniques are sometimes designated xe2x80x9cpulse-inversion imagingxe2x80x9d, xe2x80x9cphase-inversion imagingxe2x80x9d, xe2x80x9cwideband harmonic imagingxe2x80x9d, xe2x80x9cnon-linear imaging using phase cancellationxe2x80x9d, etc.
The present invention pertains to a method of coding the transmitted pressure-pulse waveform in such a way as to allow decoding the resulting echo waveforms giving essentially zero contributions from linear scatterers or tissues which do not contain contrast agent microbubbles, and significant contributions for echoes originating from contrast agent microbubbles.
The present invention relates to a method of nonlinear imaging by coding the transmitted waveforms within single transmit firings of the transducer or imaging probe. It is based on the observation that in the case of reflection by linear or essentially linear scatterers such as most tissues, individual rf-echo signals can be decoded, or deconvolved, to produce essentially zero signals, while in the case of reflection by more strongly nonlinear scatterers such as contrast agent microbubbles, the same deconvolution algorithms produce significantly non-zero signals.
In this way, a sensitive method is provided to significantly enhance the contrast between tissues and microbubbles, without paying a penalty of reducing the effective pulse-repetition frequency and frame rate.
The invention also relates to a device for carrying out the above-mentioned method, comprising means for constructing a double-pulse excitation waveform, the two pulses composing this waveform having spectra with known relative frequency dependencies with respect to one another, differing in amplitude and phase in a known fashion, this waveform being intended to be applied to an ultrasound transducer to generate an ultrasonic beam, an ultrasound transducer array connected to said excitation means, comprising one or a plurality of transducer elements, a transmitter coupled to said transducer array for pulsing said transducer elements, receiving means coupled to said transducer for receiving said echo signals, means for deconvolving returned echo signal by a first appropriate decoding function to obtain an rf-waveform, means for deconvolving returned echo signal by a second and different appropriate decoding function to obtain an rf-waveform, means for realigning in time both deconvolved rf-waveforms, means for normalizing amplitudes of said deconvolved rf-waveforms, and means for summing or otherwise combining both rf-waveforms to effectively cancel all echo components caused by linear scatterers.
The invention further relates to the use of the device for detecting and imaging the nonlinear components of ultrasound echo signals returned from scatterers within the body of human patients or animals.